Curcumin and vinblastine induce apoptosis and impair migration in human cutaneous melanoma cells

Abstract

Cancer is an important cause of lethality, and melanoma is associated with less than 10% of survival. The traditional treatment includes the use of vinblastine, and it is associated with side effects. Curcumin is extracted from Curcuma longa rhizomes, and studied in many diseases, producing a variety of effects. We investigated the role of various cellular pathways concerning apoptosis, cell cycle enzymes in melanoma cell line SK-MEL-28, after treatment with curcumin, vinblastine, or a combination of both, for 24 hours. After this, we performed cell cycle, apoptosis, wound healing assay, comet assay on cells, and evaluated nitrite accumulation (nitric oxide (NO•) byproduct). Curcumin increased cells in apoptosis and reduced the number of cells in the G1 phase. Vinblastine increased the production of nitrite, and cells in early apoptosis, mainly through the inducement of DNA damage. Cell migration was impaired in all tested groups. In conclusion, curcumin impaired migration, producing NO•, and promoting apoptosis of tumoral cells. Vinblastine also impaired cell migration and increased levels of NO•. Curcumin might be included as an adjuvant in the treatment of melanoma, and help treatment of melanoma, and further studies are needed, especially regarding the synergistic effect of curcumin and vinblastine in the treatment.

Curcumin promotes apoptosis of human melanoma cells by caspase 3

“…A recent experimental study verified that curcumin led human papillary thyroid carcinoma cells to apoptosis associated with endoplasmic reticulum stress 43 . Similar results were shown by Lunkes et al 44 who observed a significant increase in the levels of apoptosis of CM cells after treatment with 40 µM of curcumin for 24 h. For these reasons, we also searched for apoptosis induced by curcumin in CM cells. After 24 h of treatment, a significant increase in apoptotic cells at the highest concentration (100 µM) was detected.…”

“…Considering the results presented hitherto and to make this study more robust, we sought a plausible biochemical mechanism of action or signaling pathway that could explain the decrease in cell viability, apoptosis and the inhibition of cell migration. In this context, previous studies with CM reported that curcumin induces apoptosis by overproduction of ROS 12,40,44,48 . An interesting fact is that antineoplastic drugs act by exacerbating ROS levels, which induces apoptosis by activating the intrinsic pathway 49,50 .…”

“…In this context, previous studies with CM reported that curcumin induces apoptosis by overproduction of ROS. 12,40,44,48 An interesting fact is that antineoplastic drugs act by exacerbating ROS levels, which induces apoptosis by activating the intrinsic pathway. 49,50 In other CM cell lines, Kocyigit and Guler 14 and Liao et al 29 found that curcumin reduced cell proliferation and induced apoptosis by altering the redox state, increasing ROS and decreasing glutathione levels, culminating in apoptosis of neoplastic cells.…”

“…In the SK-MEL-28 cell line, Lunkes et al 44 observed an increase in nitrate levels in the supernatant and apoptosis after 24 h of treatment with 40 µM curcumin, indicating that cytotoxicity may have been induced by NOx. Interestingly, it was observed in this study that curcumin increased ROS and NOx levels at both treatment exposure times.…”

“…In other CM cell lines, Kocyigit and Guler 14 and Liao et al 29 found that curcumin reduced cell proliferation and induced apoptosis by altering the redox state, increasing ROS and decreasing glutathione levels, culminating in apoptosis of neoplastic cells. In the SK‐MEL‐28 cell line, Lunkes et al 44 observed an increase in nitrate levels in the supernatant and apoptosis after 24 h of treatment with 40 µM curcumin, indicating that cytotoxicity may have been induced by NOx. Interestingly, it was observed in this study that curcumin increased ROS and NOx levels at both treatment exposure times.…”